Dr. Paget: It is a pleasure today to introduce Dr. Daniel Libby, who is a Clinical Professor of Medicine at the Weill Medical College of Cornell University. Dr. Libby is a renowned pulmonary specialist who has helped us over the years in taking care of our patients with various rheumatologic, autoimmune, and connective tissue diseases and their pulmonary problems.

Dr. Libby, what is there about the lung that makes it so prone to being attacked, invaded, affected by the diseases that we take care of over here at HSS?

Dr. Libby: I think that there are two things that make the lung involved in a lot of peripheral disorders. One is, of course, that the lung is a filter. It filters both the air that we breathe constantly, so that anything in the environment has the potential to affect the body first in the lungs. The second point is that the lungs receive the entire cardiac output of blood supply, so that if there is an immune problem or infectious problem somewhere in the body, very often the lung is affected. That would be a general answer to the question of why the lungs get involved so frequently with rheumatologic problems.

Dr. Paget: Many of the diseases that we deal with at HSS are immunological disorders, and the lung certainly plays a role in immunology, in filtering, and also in the battlefront between the invaders and the inner part of the body. Is the lung a very effective organ in protecting us in those ways?

Dr. Libby: I would say yes. The lung is very effective. When I say the lung, I mean the entire respiratory system, from the tips of the nerves in the mouth, to all the structures inside the bronchial tubes, and the microscopic hairs called cilia and the mucous that is produced. These are all aspects of the respiratory system that help us fight infections, so that if something is breathed in from the air we are able to clear it.

Internally, the lungs are pretty much like any other part of the body. They contain lymph glands that help fight infections or react to problems in the body. The lung has a fairly limited number of responses that it can mount against various insults. We will probably touch upon those as we talk, but the lung responds in a similar way to a variety of different insults or invaders from the outside.

Dr. Paget: You alluded a moment ago to infection, and that is important because not only can some of the disorders we will talk about in a moment directly affect the lung, but the therapies that we give for those disorders can set patients up for infections.

Dr. Libby: Absolutely. Take, for example, the disease lupus. How does it affect the lung? Probably the most common way lupus affects the lung is that the lung is exposed to a lot of different infections in people with lupus. Thus, it's not so much the lupus itself, but both the treatment of the lupus and the underlying disease make the patient more prone to infection. So if people have a pulmonary problem and they have lupus, there is an excellent chance that there is infection. There doesn't have to be, but that often is the case.

Dr. Paget: Before discussing these various illnesses, what are the parts of the lung that we can break up for the discussion, fully understanding that one or more of them can be involved in any disorder? What are the players that we are dealing with?

Dr. Libby: The players really are the different anatomic parts of the respiratory system. Let's start from the outside-in. The pleura, or the lining of the lung, is commonly involved in disorders that you might describe as pleurisy. It can get involved through inflammation, and fluid can accumulate. Next, the substance of the lung, the lung parenchyma itself, can be involved in a variety of different ways. As a generic term, when we say the lung is inflamed or infected, we are discussing the lung substance, and the patient has pneumonitis or pneumonia.

Also commonly involved are the bronchial tubes and the little bronchial tubes called bronchioles. They can get obstructed or scarred, and this can cause a problem. Then, further up towards the mouth, even the vocal cords can get involved, because the vocal cords have little joints called cricoarytenoid joints, which can be involved in certain rheumatologic disorders. Also, in certain disorders, the production of saliva, which is an important aspect of our defense against infections, can be inhibited by disorders such as Sjögren's syndrome.

Then a little higher up are the sinuses - the paranasal sinuses - which can be affected in certain disorders. So, really, virtually any part in the respiratory system can be affected.

Dr. Paget: So let's go into them and try to find out what anatomical components can be involved, either singly or together. In rheumatoid arthritis, center stage is still the joint. A certain percentage of patients develop what are called extra articular manifestations. What are the typical manifestations that you see as a pulmonologist with regard to rheumatoid arthritis?

Dr. Libby: Rheumatoid arthritis can affect the lung in many ways. One of the ways is that it can cause a type of pleurisy, a little fluid accumulation outside the lung. It is not often a large amount of fluid, but it can be large. It can be confused with other problems, such as infection or cancer, but generally by a process of elimination, the analysis of that fluid, and the general condition of the patient tell us that it is related to the rheumatoid arthritis and not some infection. So rheumatoid pleurisy, or rheumatoid pleural effusion, is one manifestation.

Another very common problem would be involvement of the substance of the lung itself. In this category, there are a few different ways that rheumatoid arthritis can affect the lung. One is called interstitial lung disease, where the substance of the lung is affected diffusely with scar tissue and/or inflammation.

We have to be careful in dealing with pneumonitis or interstitial lung disease in rheumatoid arthritis, whether it's the rheumatoid arthritis itself that is affecting the lung, the treatment of the rheumatoid arthritis (the various drugs can also cause inflammation in the lung, or, of course, infection. All can give similar findings on x-ray or clinically.

Another way that rheumatoid arthritis can affect the substance of the lung is to cause little spots or nodules in the lung. Rheumatoid nodules can form in other parts of the body, like the skin, but in the lung, they often cause confusion because one isn't sure. Is it a rheumatoid nodule, is it infection or is it cancer? So sometimes a biopsy has to be performed to differentiate among these possibilities.

There is another manifestation of rheumatoid arthritis in the lung called fibrobullous disease, where there are little cysts, usually at the top of the lung, that can be a problem.

Then we can move from the substance of the lung into the bronchial tubes. Sometimes rheumatoid arthritis involves the little bronchial tubes called bronchioles and causes a condition, which can be indistinguishable from emphysema or chronic obstructive pulmonary disease, called rheumatoid bronchiolitis.

Another manifestation, as I alluded to before, is involvement of the vocal cords with the cricoarytenoid joints, called cricoarytenoid arthritis. In that case, a patient might complain of hoarseness or shortness of breath. That is a fairly uncommon manifestation.

Dr. Paget: As a rheumatologist, I am aware that these are very uncommon manifestations. To a pulmonary doctor, when you see them, obviously they are 100% of the patients that you are seeing at the moment. Let's use rheumatoid arthritis as an exemplar to display the tools you have at hand to make a diagnosis, from the simple to the more invasive.

Dr. Libby: Let's take a patient who has developed shortness of breath as a symptom, and maybe a dry cough. The physical examination might display some findings in the lungs, some fine crackle or "rales" as we term them. The chest x-ray might show some diffuse changes in the lungs.

You might refer the patient to me with a possible diagnosis of interstitial lung disease, perhaps related to rheumatoid arthritis. Then I would query the patient about medications they have been on, other symptoms, travel, things that might indicate some time of unusual infection. Then I might order a CAT scan to help me see what the findings are in the lung. That sometimes helps differentiate the types of interstitial lung disease.

And then, finally, we might decide, if it's important enough, that some type of tissue biopsy is necessary. This can be performed either bronchoscopically, with an instrument inserted through the nostril after local anesthesia with sedation or, on occasion, it is necessary to get a larger piece of lung tissue and general anesthesia is required. This minimally invasive surgery is called video assisted thoracoscopic biopsy.

So those would be examples of some of the tools.

We also test the functional aspects of the patient. Very often we will order breathing tests or pulmonary function tests, which can be used as objective ways of following the progress of the disease or the therapy for the disease.

Dr. Paget: We will come back in a moment to therapeutic options, because they in some ways overlap a bunch of the disorders we will talk about. Let's move on for a moment to lupus. How is lupus either the same or different from rheumatoid arthritis with regard to its lung manifestations?

Well, some of the manifestations can be identical. In lupus, the patients can have interstitial lung disease. In fact, there are rare cases where the interstitial lung disease seems to be the major part of the lupus. However, as a general rule with lupus, interstitial lung disease isn't as common as it is with rheumatoid arthritis.

Dr. Libby: In lupus, more commonly the patient might have pulmonary manifestations such as pleurisy, which would be heralded not by the symptoms of shortness of breath on exertion, but rather by some chest pain with deep breath. So that that would be the symptom one might expect from lupus causing pleurisy.

Also with lupus, perhaps a little bit more commonly than with rheumatoid arthritis and other rheumatologic disorders, there can be fairly acute problems in the lung, possibly influenced by the lupus therapy, such as opportunistic infections, and the lupus itself can affect the lung fairly suddenly with an acute pneumonia, which can be very profound.

Dr. Paget: As you're implying as well, patients with lupus or rheumatoid arthritis are humans and are subject to all the other scenarios of possible problems. So they can get infections. The lupus patients can even have pulmonary emboli, and so you really have to broaden your concept of possibilities because it is a multisystem disorder.

Dr. Libby: Absolutely. As you said, you have to look at the whole patient. If patients have been lying in bed, they might be prone to pulmonary emboli - as they might if they have antiphospholipid syndrome, which predisposes to clots.

Dr. Paget: What is your armamentarium in rheumatoid arthritis and lupus? Obviously, it's my job to control the rest of the disease, and if infection is ruled in you treat it - but what do we have in our armamentarium to treat lung problems?

Dr. Libby: If we are talking about a problem such as pleurisy associated with lupus, then it often would simply be a buck-up in the dose of steroids or the introduction of steroids to control that. If we are talking about progressive interstitial lung disease, then again, it might require introduction or increase in steroid dosage and cessation of medications that might introduce interstitial lung disease, such as methotrexate.

In addition, we occasionally add drugs that you might or might not use for rheumatoid arthritis to treat the lung problems, such as azathioprine. We have a certain armamentarium, and there is a lot of overlap with what you use to treat the underlying rheumatoid arthritis.

Dr. Paget: So we are equally aggressive to the aggressiveness of this disorder and we up the ante depending upon how it is presented.

Dr. Libby: Yes, the focus is its impact on the person's life overall. For example, if the person has interstitial lung disease but it's not affecting daily life too much, I wouldn't get too aggressive about treating it. But if it is affecting lifestyle greatly, I would be more aggressive in looking at it.

Dr. Paget: Let's move on to another connective tissue disorder that has a slightly different personality when it comes to the lung, and that's scleroderma.

Dr. Libby: Scleroderma can be devastating in its pulmonary manifestations. Sometimes it can, however, present just as a curiosity with a finding on a chest x-ray that the patient and doctor really are not aware of. But to turn our attention to scleroderma there are different ways that it can affect the respiratory system. One is, again, interstitial lung disease or scar tissue in the lung, very similar in many ways to the manifestations that we mentioned in rheumatoid arthritis and lupus.

Another manifestation in the lung would be a condition called pulmonary hypertension. This is where the pressure in the pulmonary blood vessels, that is the blood vessels that connect the heart to the lungs, can go up. This is a result of inflammation or scar tissue in the tiny little arteries that feed the lung, and this can cause the patient to notice symptoms like shortness of breath, faintness or loss of consciousness. It can cause cardiac arrhythmias and could even be fatal.

It is a difficult condition to treat. One has to think of it -- have a high suspicion of it -- in a patient with scleroderma, because very often there isn't a chest x-ray finding or physical exam finding that automatically points to it. So if you have a patient with scleroderma, often a woman, but not always, on the young side, who has symptoms of unexplained shortness of breath, loss of consciousness, near fainting or palpitations, you should think of the possibility of pulmonary hypertension because it can be treated.

There are other manifestations of scleroderma in the lung. Scleroderma very often affects swallowing; the esophagus can be affected in scleroderma. Because of that, the lungs can get secondarily involved with gastric juice or fluid that is aspirated down the wrong way.

Dr. Paget: Finally, another type of disorder potentially damaging to the lung is Wegener's granulomatosis. That is yet a different kind of presentation. Maybe you can tell us a little bit about that.

Dr. Libby: Wegener's granulomatosis is a thoroughly uncommon disease. It tends to affect men more than woman, unlike some of the other rheumatologic disorders. It is a disease of inflammation around the blood vessels. It can affect many different parts of the body, but since today we are talking about the respiratory system, I will concentrate on that.

Wegener's can affect the respiratory system in several ways. One, it can involve the sinuses. It can cause sinusitis, and it can be difficult to distinguish from infectious sinusitis. But if the person has involvement of many sinuses and it is difficult to treat this disorder, Wegener's should be thought of.

It can also involve the upper airway, that is, parts of the respiratory system like the voice box or larynx or the bronchial tubes. It can cause narrowing or ulceration in these structures. Finally, it can involve the substance of the lung itself. It can cause spots on the lung, which can be confused with cancer or infection; sometimes the spots are filled with air in their cavities.

There are times when Wegener's presents with interstitial lung disease, but it's more likely for Wegener's granulomatosis to produce discreet spots or cavities in the lung.

Dr. Paget: How do we treat that?

Dr. Libby:

First, we differentiate it from other disorders such as infection. Once we have done that, we often require a tissue biopsy to make a definite diagnosis of Wegener's. Also, we have to evaluate the whole patient, because Wegener's often will involve other parts of the body that need special attention such as the kidneys. But there are many cases of Wegener's where it seems to be confined to the respiratory system. If it seems to be a disorder that is progressive and not going away on its own, then it is treated with a variety of medications, often a combination of steroids with cytotoxic drugs like azathioprine or cyclophosphamide, and other medications now available as well.

Dr. Paget: What do you see on the horizon from a diagnostic point of view? Are there new types of imaging studies that will give us better ideas about the pathology?

Dr. Libby: I think the use of the CAT scan has been very important with high resolution imaging. This is helpful in differentiating infection from an underlying rheumatologic disorder. Often studies such as PET scans (positron emission tomography) in this setting are not that helpful. They are useful in cases where you have to differentiate malignancy from inflammatory disorders, but there isn't enough experience with PET scanning at this point to really say that it is going to be that helpful.

We often rely on our colleagues, the rheumatologists, to get the right blood test to help us. Blood tests can be helpful in telling us if the rheumatologic disorder is active. For example, in Wegener's, a person might present with spots on the lung, and if someone thinks of the diagnosis they will draw the ANCA level, often before the patient sees me. It makes my job a lot easier. Then there are blood tests that can be used in deciding about fungal infections and that sort of thing.

Those are some of things that we have. Imaging is important, but it never takes the place of good history, physical, blood tests, adjunctive techniques that we have.